Methods of inhibiting cataracts and presbyopia

Abstract

Described herein are methods of inhibiting or reversing the progression of cataract formation or presbyopia in an eye by administering a β L -crystallin electrostatic interaction inhibitor. Both presbyopia and cataracts are caused by aggregation of the soluble crystalline lens proteins called the crystallins, particularly β L -crystallin. It has been found that the aggregation of β L -crystallin is an electrostatic phenomenon and that electrostatic interaction inhibitors can be employed to prevent the formation of β L -crystallin aggregates as well as to deaggregate already formed aggregates.

The invention claimed is: 
     
       1. A method of inhibiting or reversing in situ the progression of cataract formation in an eye comprising
 contacting the crystalline lens in situ in the eye with an effective cataract-inhibiting amount of an ophthalmic composition comprising at least one β L -crystallin electrostatic interaction inhibitor, wherein the β L -crystallin electrostatic interaction inhibitor is an organic or inorganic salt selected from NH 4 Cl, CaCl 2 , sodium acetate, potassium acetate, ammonium acetate, sodium citrate, potassium citrate, ammonium citrate, sodium sulphate, potassium sulphate, ammonium sulphate, calcium acetate, ethylammonium nitrate, sodium formate, sodium ascorbate, magnesium gluconate, sodium gluconate, tromethamine hydrochloride, sodium succinate, and combinations thereof. 
 
     
     
       2. A method of inhibiting or reversing the progression of cataract formation in an eye comprising
 contacting the eye with an effective cataract-inhibiting amount of an ophthalmic composition comprising at least one β L -crystallin electrostatic interaction inhibitor, wherein the β L -crystallin electrostatic interaction inhibitor comprises an organic salt containing a cation and an anion, wherein the cation and the anion are each independently an aliphatic group with the length of the aliphatic moiety of four to fifteen carbon atoms. 
 
     
     
       3. The method of  claim 2 , wherein the organic salt comprises an ionic liquid. 
     
     
       4. The method of  claim 1 , wherein the β L -crystallin electrostatic interaction inhibitor is in the form of an ophthalmic composition comprising at least one ophthalmically acceptable vehicle. 
     
     
       5. The method of  claim 4 , wherein the ophthalmic composition is an eye drop. 
     
     
       6. The method of  claim 4 , wherein the ophthalmic composition is an ophthalmic device. 
     
     
       7. The method of  claim 6 , wherein the ophthalmic device is a contact lens or a punctal plug. 
     
     
       8. The method of  claim 2 , wherein the β L -crystallin electrostatic interaction inhibitor is in the form of an ophthalmic composition comprising at least one ophthalmically acceptable vehicle. 
     
     
       9. The method of  claim 8 , wherein the ophthalmic composition is an eye drop. 
     
     
       10. The method of  claim 8 , wherein the ophthalmic composition is an ophthalmic device. 
     
     
       11. The method of  claim 10 , wherein the ophthalmic device is a contact lens or a punctal plug. 
     
     
       12. The method of  claim 3 , wherein the β L -crystallin electrostatic interaction inhibitor is in the form of an ophthalmic composition comprising at least one ophthalmically acceptable vehicle. 
     
     
       13. The method of  claim 12 , wherein the ophthalmic composition is an eye drop. 
     
     
       14. The method of  claim 12 , wherein the ophthalmic composition is an ophthalmic device. 
     
     
       15. The method of  claim 14 , wherein the ophthalmic device is a contact lens or a punctal plug. 
     
     
       16. The method of  claim 3 , wherein the ionic liquid is an N′-alkyl or N′-(ω-hydroxy-alkyl)-N-methylimidazolium chloride, a tri-isobutyl(methyl) phosphonium p-toluenesulfonate, a 1-ethyl-3-methylimidazolium tetrafluoroborate, a 1-butyl-3-methylimidazolium chloride, a 1-hexyl-3-methylimidazolium chloride, a 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, a 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, a tetraethylammonium bromide, an n-butylpyridinium chloride, a tetrabutylphosphonium bromide, a benzyltriethylammonium chloride, a 1-ethyl-3-methylimidazolium chloride, a 1-butyl-2,3-dimethylimidazolium tetrafluoroborate, a 1,3-dimethylimidazolium methyl sulfate, a 1-butyl-3-methylimidazolium trifluoroacetate, a 1-butyl-3-methylimidazolium chloride, a 1-butyl-3-methylimidizolium 2(2-methoxyethoxy)ethylsulfate, a 1-butyl-1-methylpyrollidinium dihydrogenphosphate, or a combination thereof.